A Study of the Safety and Efficacy of MK-3577 in Participants With Type 2 Diabetes Mellitus (MK-3577-009)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo to MK-3577; Drug: MK-3577; Drug: Metformin; Drug: Placebo to Metformin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00868790

3577-009

CTRI/2009/091/000614 (Registry Identifier)

2009_564 (Other Identifier)

Details and patient eligibility

About

This study assessed the safety and efficacy of MK-3577. The primary efficacy hypothesis was that, after 4 weeks of treatment, either the morning (AM) administration or the evening (PM) administration of MK-3577 provides superior reduction of 24-hour weighted mean glucose (WMG) levels compared to placebo (PLA). The primary safety hypothesis was that MK-3577 is well tolerated compared to placebo.

Full description

This was a 4-period/5-treatment crossover study. Each period was 4 weeks. The 5 treatments consisted of MK-3577 10 mg once daily (QD) in the AM, MK-3577 6 mg QD in the evening (PM), MK-3577 25 mg twice daily (BID), metformin 1000 mg BID, and placebo to MK-3577/placebo to metformin. Participants were to be randomized to one of 14 treatment sequence arms. A subset of participants in each group was to domicile (stay overnight) at selected clinical sites at Baseline, Week 4 (end of Period 1), and Week 8 (end of Period 2) to undergo 24-hr blood sample.

Enrollment: 118 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant has type 2 diabetes
• Participant is either not taking antihyperglycemic medications for the last 10 weeks OR is taking a single oral antihyperglycemic medication (but not a Peroxisome Proliferator-Activated Receptor gamma [PPARg] agonist) OR is taking a low-dose combination oral antihyperglycemic medication (not a PPARg agonist) at dose less than or equal to 50% of the maximum dose
• Female participant is unable to have children

Exclusion criteria

• Participant has a history of type 1 diabetes or ketoacidosis
• Participant has been treated with a PPARg agonist in the last 12 weeks
• Participant has been treated with insulin in the last 12 weeks
• Participant has had prescription lipid-modifying drug therapy in the last 12 weeks
• Participant has a history of coronary artery disease
• Participant has had a stroke or transient ischemic attack
• Participant has congestive heart failure

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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118 participants in 14 patient groups

PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)

Experimental group

Description:

Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.

Treatment:

Drug: Placebo to MK-3577

Drug: Placebo to Metformin

Drug: MK-3577

MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.

Treatment:

Drug: Placebo to MK-3577

Drug: Placebo to Metformin

Drug: MK-3577

MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed MK- 3577 25 mg BID for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4.

Treatment:

Drug: Placebo to MK-3577

Drug: MK-3577

MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.

Treatment:

Drug: Placebo to MK-3577

Drug: MK-3577

PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5)

Experimental group

Description:

Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4.

Treatment:

Drug: Placebo to MK-3577

Drug: MK-3577

MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4.

Treatment:

Drug: Placebo to MK-3577

Drug: MK-3577

MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.

Treatment:

Drug: Placebo to MK-3577

Drug: MK-3577

MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4.

Treatment:

Drug: Placebo to MK-3577

Drug: MK-3577

PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)

Experimental group

Description:

Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.

Treatment:

Drug: Placebo to MK-3577

Drug: Placebo to Metformin

Drug: MK-3577

MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.

Treatment:

Drug: Placebo to MK-3577

Drug: MK-3577

MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.

Treatment:

Drug: Placebo to MK-3577

Drug: Placebo to Metformin

Drug: MK-3577

MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12)

Experimental group

Description:

Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4.

Treatment:

Drug: Placebo to MK-3577

Drug: MK-3577

PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)

Experimental group

Description:

Domiciled participants were to receive oral treatment with dose-matched placebo to metformin (METF) for 4 weeks during Period 1, followed by metformin 1000 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Participants in this arm were administered metformin placebo during Period 1 and active metformin during Period 2.

Treatment:

Drug: Placebo to MK-3577

Drug: Placebo to Metformin

Drug: Metformin

Drug: MK-3577

METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)

Experimental group

Description:

Domiciled participants were to receive oral treatment with metformin 1000 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to metformin for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. Participants in this arm were administered active metformin during Period 1 and metformin placebo during Period 2.

Treatment:

Drug: Placebo to MK-3577

Drug: Placebo to Metformin

Drug: Metformin

Drug: MK-3577